Our previous work has estalbished behavioral and biochemical asymmetry to ischemic lesion or focal suction lesions of the left or right cerebral cortex in the rat. This proposed research project will study the neuro and behavioral pharmacology of the mechanisms responsible for neurochemical and behavioral asymmetry. The first experiment seeks to further establish the similarity of focal suction and ischemic lesions by determining if daily administration of desmethylimipramine to rats will prevent the development of spontaneous hyperactivity produced by right fronto-cortical suction lesions as it does in right vascular lesioned animals. The second study will determine the effect of unilateral fronto-cortical doopaminergic lesions. The second series of experiments seeks to establish the class(es) of receptor(s) involved in he production of post lesion hyperactivity. These studies will involve the chroic 14-day intraventricular infusion of various adrenergic and cholinergic agonists or antagonists by means of implanted osmotic pumps. Administered in preliminary doses which produce tissue steady state levels of 10KD will be alpha 1 (al) agonists (AG) methoxamine and WB-4101, antagonist (ANT) prazocine; a2 AG, clonidine, ANT yohimbine; B1 AG, isoproterenol and ANT, propranalol and dihydroalprenalol; muscarinic AG, oxytremorine and ANT scopalamine. The 30-day length of the experiment will permit the evaluation of receptor sub and supersensitivity following pump exhaustion. The third series of experiments attempts to extend the range of potentially lateralized behaviors beginning with DRL and multiple FI-FR schedules of reinforcement while refining measures of our current technique. The proposed study will advance our knowledge of neural asymmetry and the elucidate some of the mechanisms underlying the pathophysiology of stroke.